ASH: Transplant Strategy Falls Short in Multiple Myeloma

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Explain that in patients with standard-risk multiple myeloma, an attempt to harness the so-called graft-versus-myeloma effect has come up short.

ORLANDO -- In patients with standard-risk multiple myeloma, an attempt to harness the so-called graft-versus-myeloma effect has come up short, a researcher said here.

The effect -- seen when patients get a stem cell transplant from a sibling donor -- is an immunologic response that, at least in principle, has the potential to be curative, according to Amrita Krishnan, MD, of City of Hope Medical Center in Duarte, Calif.

But in a randomized trial testing the theory, treatment-related mortality outweighed the benefit after three years of follow-up, Krishnan told reporters at the American Society of Hematology meeting.

The study looked at so-called tandem transplants in patients who had an immune system-matched sibling donor and those who didn't.

Patients with no donor were given two separate autologous transplants of their own stem cells, an "auto-auto transplant," Krishnan said.

Those with a donor, on the other hand, were first given their own cells followed later by a transplant of the donor cells, an "auto-allo transplant."

Auto-auto transplants have been shown to improve progression-free survival, but the auto-allo version, Krishnan said, has the potential to do even better because of the graft-versus-myeloma effect.

"That's the huge benefit of an allo-transplant, which ultimately may lead to cure for these patients," Krishnan said.

The barrier is that an allo-transplant is associated with treatment-related mortality, which, in the early days of the treatment, reached as high as 50%, Krishnan said.

To investigate whether more modern techniques had changed the picture, she and her colleagues enrolled 710 patients from 43 U.S. centers between December 2003 and March 2007 and assigned them to the auto-auto or auto-allo arms depending on whether they had a sibling donor.

All patients had a conditioning regimen of high-dose melphalan (Alkeran) followed by the first autologous transplant. Between 60 and 120 days later, they had the second transplant.

Those getting an allogeneic transplant had a nonmyoablative conditioning regimen of a single dose of whole body radiation, followed by the stem cells. Those getting a second autologous transplant had a second round of high-dose melphalan, followed by the cells.

After three years, the researchers found no significant differences in progression-free survival, overall survival, or the cumulative incidence of progression or relapse. Specifically:

The probability of progression-free survival was 46% for the auto-auto arm and 43% for the auto-allo arm.

Overall survival was 80% for auto-auto and 77% for auto-allo.

Cumulative incidence of progression or relapse was 46% for the auto-auto arm and 40% for the auto-allo arm.

On the other hand, Krishnan said, there was a difference in treatment-related mortality -- 4% for the auto-auto arm and 12% for the auto-allo arm, which was significant at P<0.001.

That 12% is a major advance on the 50% seen in earlier tests of allogeneic transplants, she said, but more needs to be done. The investigators are now trying to improve methods and also to see if there are subgroups of patients that will do better, Krisnan said.

What the analysis needs is more follow-up, said Armand Keating, MD, of the University of Toronto and the society's vice president. He was not involved in the research but moderated a press conference at which it was presented.

"You probably can't cure any patients with tandem autos," he told MedPage Today, "so the question is whether you can cure some with tandem auto-allo transplants."

Even though the survival curves seem identical after three years, he said, it could be that the immunologic effect of the allo-transplant will start to kick in down the road.

The trial was supported by the Blood and Marrow Transplant Clinical Trials Network and the NIH.

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